AJG

GUIDELINES ACG Clinical

[AUTHOR INSIGHT] PANCREATIC CYSTS: AN INCREASINGLY COMMON CONCERN

Grace H. Elta, MD, FACG, Brintha K. Enestvedt, MD, MBA, Bryan G. Sauer, MD, MSc, FACG (GRADE Methodologist), Anne Marie Lennon, MD, PhD, FACG  PANCREATIC CYSTS ARE BEING DIAGNOSED MUCH MORE OFTEN and are present in up to 40% of individuals over the age of 70! Given that pancreatic cancer incidence is not changing, this increase in cyst diagnosis is most likely due to the improved quality and more frequent performance of CT and MRI exams. Most pancreatic cysts are found incidentally and are asymptomatic. The most common cysts are side branch intra-ductal papillary mucinous neoplasms (IPMNs). Although side branch-IPMNs do have malignant potential, the vast majority will never develop into pancreatic cancer. The surveillance efficacy for the prevention of pancreatic cancer is unknown and it is costly. Hence the management conundrum and the many differences in existing national and international pancreatic cyst guidelines. The new ACG Guideline on the Diagnosis and Management of Pancreatic Cysts is available online.

The first step in pancreatic cyst management is to determine cyst type. They can be neoplastic or non-neoplastic (pseudocysts), with the neoplastic ones further categorized as mucinous, IPMNs and mucinous cystic neoplasms (MCNs), vs. non-mucinous, which are primarily serous cystadenomas. Other rare pancreatic cyst types are also discussed in the guideline. MRI/MRCP and CT scan are the most commonly used imaging modalities, although both suffer in diagnostic accuracy for determining cyst type, with accuracy of 4050%. The addition of endoscopic ultrasound with FNA may help diagnose pancreatic cyst type when the diagnosis is unclear from clinical history and imaging.

The second step is to determine if the cyst is causing symptoms—which is rare—or carries any features worrisome for cancer (see Table 3). Because many incidental pancreatic cysts are found in elderly individuals, it is also important at this step to assess whether the patient is a surgical candidate and would be interested in pursuing surgery. Pancreatic surgery carries significant morbidity and some mortality. If the patient is not fit for surgery, no further evaluation or surveillance should occur. Patients with symptomatic neoplastic cysts or imaging features worrisome for cancer should be referred to a multi-disciplinary pancreatic cancer center. Many of these patients may not require surgery, but a careful, multi-discipline opinion is valuable.

When the diagnosis of cyst type or the decision to operate remains unclear, EUS with cyst sampling can be helpful. Elevated cyst fluid CEA (>192 ng/ml) is suggestive of a mucinous cyst; if this is still nondiagnostic, analysis of cyst fluid KRAS and GNAS mutations can be used in diagnosing mucinous cysts. However, like cyst fluid CEA, they are not helpful in diagnosing cancer or high-grade dysplasia. EUS is also quite accurate at differentiating cyst wall nodules from mucin collections. Cyst fluid cytology showing dysplasia or cancer is very helpful, although most specimens are paucicellular and non-diagnostic. The role of cyst fluid genomics, cyst wall biopsy or confocal microscopy remains uncertain at this time. The treatment of symptomatic or worrisome cysts continues to be surgery. The possible role of cyst ablation techniques requires more study.

Once an asymptomatic pancreatic cyst is determined to most likely be a mucinous cyst, a discussion with the patient about potential surveillance should occur. The low risk of malignancy and unknown benefit of surveillance should be made clear. If the patient wishes to proceed and there are no high-risk features, MRI/MRCP is the usual choice for surveillance; EUS is an excellent alternative if the patient is unable or unwilling to undergo MRI. CT can also be utilized, although it is usually avoided due to radiation dose. Cyst surveillance intervals continue to be determined by cyst diameter, even though cyst size is only one measure of risk. This guideline gives practical recommendations on how often surveillance should occur. It also recommends that surveillance intervals may be lengthened after size stability is established. Given evidence that the risk of cancer does not diminish with time, surveillance should be continued until the patient is no longer a surgical candidate.

Read the Guideline rdcu.be/I71Q

Listen to the AJG Author Podcast gi.org/ajgpodcasts/Elta

TABLE 3. HIGH-RISK CHARACTERISTICS FOR MUCINOUS PANCREATIC CYSTS

Symptoms

Jaundice secondary to the cyst Acute pancreatitis secondary to the cyst Elevated serum CA 19-9 when no benign cause for elevation is present

Imaging findings

Mural nodule or solid component within the cyst or pancreatic parenchyma Main pancreatic duct diameter of >5 mm Change in main duct caliber with upstream atrophy Size > 3 cm Increase in cyst size > 3 mm/year

Cytology

[AUTHOR INSIGHT] ALCOHOLIC LIVER DISEASE

Vijay H. Shah, MD, FACG, Ashwani K. Singal, MD, MS, FACG, Ramon Bataller, MD, PhD, FACG, Joseph Ahn, MD, MS, FACG (GRADE Methodologist), Patrick S. Kamath, MD  LIVER CIRRHOSIS IS THE 12TH LEADING CAUSE OF MORTALITY IN THE UNITED STATES and at least one half of cases of liver cirrhosis relate to an alcohol-related etiology. With recent advances in management of viral hepatitis-related cirrhosis, it is important for providers to be up to date in management of alcohol-related etiologies because this problem is likely to continue for the foreseeable future.

EARLY DIAGNOSIS

The first step in diagnosing alcohol-related liver disease is to try to make the diagnosis at an earlier stage than cirrhosis. This requires asking about alcohol use and addiction and providing input, guidance and feedback to the patient at the time of initial screening. A number of tools are available for this, and the key is to ask the questions. Not all patients who consume excess amounts of alcohol actually develop alcoholic liver disease, probably only about 20-30% of patients do so. There may be some genetic factors that predispose individuals as well as other co-variables such as obesity and co-existing forms of liver insults such as viral hepatitis. In individuals who consume excess amounts of alcohol, it is prudent to check AST, ALT and, if elevated, then to perform an ultrasound of the liver as initial testing.

JAUNDICE

In individuals who present with jaundice in the setting of excess alcohol consumption, it is important to consider alcoholic hepatitis in the differential diagnosis. Laboratory profile will usually reveal AST/ALT ratio of greater than 1.5 with transaminase levels generally less than 300.

LIVER BIOPSY

The guideline outlines an approach to liver biopsy in which liver biopsy can be pursued in the setting where testing is not definitive for alcoholic hepatitis and/or when testing suggests potential alternative etiologies.

ASSESSING PROGRESS IN ALCOHOLIC HEPATITIS

After the diagnosis of alcoholic hepatitis is made, it is important to use available nomograms to assess prognosis. The Maddrey Discriminant Function score is the most time-tested nomogram, however, many providers are moving to more modern nomograms, especially MELD score. A MELD score over 20 denotes severe alcoholic hepatitis that may warrant pharmacologic therapy.

PHARMACOLOGIC THERAPY

In terms of pharmacologic therapy, recent studies have shown that pentoxifylline is unlikely to be providing benefit in patients with alcoholic hepatitis and should no longer be used in that setting. Corticosteroids do provide a small survival benefit but only for one-month survival. Therefore, they could be utilized in cases where there are not contraindications to corticosteroids. However, clearly better therapies are needed for the future and an emphasis on abstinence needs to be pursued to improve survival beyond one month.

LIVER TRANSPLANTATION

There has been recent momentum in the area of liver transplantation for patients with alcoholic hepatitis, however, it should be emphasized that the majority of patients with alcoholic hepatitis do not fit the criteria for liver transplantation. It should be considered only in individuals who have very strong social support, lack of psychiatric comorbidities, are presenting with their first bout of alcoholic hepatitis, have not failed prior to treatment efforts for addiction, and who have not responded to pharmacotherapy for their alcoholic hepatitis. This constitutes a small percentage of the patients with alcoholic hepatitis.

Read the Guideline rdcu.be/I8ac

Listen to the AJG Author Podcast gi.org/ajgpodcasts/shah

FIGURE 1. DISEASE SPECTRUM OF ALCOHOLIC LIVER DISEASE

Alcoholic hepatitis Alcoholic hepatitis Alcoholic hepatitis Alcoholic hepatitis Alcoholic hepatitis Alcoholic hepatitis

RISK FACTORS: Amount alcohol Obesity PNPLA3 variations Smoking, coffee Viral hepatitis Amount alcohol Obesity PNPLA3 variations Smoking, coffee Viral hepatitis Risk factors: Amount alcohol Obesity PNPLA3 variations Smoking, coffee Viral hepatitis Risk factors: Amount alcohol Obesity PNPLA3 variations Smoking, coffee Viral hepatitis Risk factors: Amount alcohol Obesity PNPLA3 variations Smoking, coffee Viral hepatitis Risk factors: Amount alcohol Obesity PNPLA3 variations Smoking, coffee Viral hepatitis Risk factors:

Alcoholic Liver Disease Alcoholic Liver Disease Alcoholic Liver Disease Alcoholic Liver Disease Alcoholic Liver Disease

Chronic alcohol abuse Chronic alcohol abuse Chronic alcohol abuse Chronic alcohol abuse Chronic alcohol abuse Chronic alcohol abuse

90–95%90–95% 90–95% 90–95% 90–95% 90–95% 20–40%20–40% 20–40% 20–40% 20–40% 20–40%

Normal liver Normal liver Normal liver Normal liver Normal liver Normal liver

Steatosis Steatosis Steatosis Steatosis Steatosis Steatosis Figure 1 . Disease spectrum of alcoholic liver disease.Figure 1 . Disease spectrum of alcoholic liver disease.Figure 1 . Disease spectrum of alcoholic liver disease.Figure 1 . Disease spectrum of alcoholic liver disease.Figure 1 . Disease spectrum of alcoholic liver disease.

Fibrosis Fibrosis Fibrosis Fibrosis Fibrosis Fibrosis

8–20%8–20% 8–20% 8–20% 8–20% 8–20%

Cirrhosis Cirrhosis Cirrhosis Cirrhosis Cirrhosis Cirrhosis

3–10%3–10% 3–10% 3–10% 3–10% 3–10%

HCC HCC HCC HCC HCC HCC